The overall goal of this project is to investigate the mechanisms of control of enzymes that may be important determinants of the effects of catecholamines and other drugs and hormones on contractility and glycogen metabolism in cardiac muscle, and in other types of contractile tissue. This has been the primary interest of our group over the past years, and our research supported through Nov. 30, 1978 by HL-12373 has resulted in significant increases in the understanding of biochemical control of cardiac adrenergic responses. We will investigate: 1) the coupling of activated adrenergic receptors to the intracellular formation of cyclic AMP; 2) the characteristics, functions and control by calcium of cardiac phosphorylase kinase; 3) the role of the heat-stable protein kinase inhibitor in controlling cyclic AMP dependent protein kinase; 4) the effect of secondary or multiple sites of phosphorylation on the activity of key enzymes and regulatory proteins. These investigations are all based on the hypothesis that the various regulatory mechanisms to be investigated in vitro are important in the control of contractility and metabolism in intact cardiac tissue. Enzymes and regulatory proteins will be purified from heart or skeletal muscle in order to evaluate potential sites of regulation by phosphorylation, calcium, etc. Adrenergic control of contractility, regulatory enzymes, and glycogen metabolism will also be assessed in perfused hearts and isolated papillary muscles in order to correlate physiological and biochemical changes.